α-硫辛酸通过激活ALDH2减轻酒精诱导的大鼠H9c2细胞损伤

目的:研究α-硫辛酸(α-lipoic acid,α-LA)对酒精所致H9c2大鼠心肌细胞损伤的作用及其可能机制。方法:建立H9c2心肌细胞的酒精损伤模型,并将其分成4组:对照组、酒精组、α-LA组和酒精+α-LA组。构建乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)高转染心肌细胞,将其分成6组:对照组、酒精处理H9c2心肌细胞组、酒精+α-LA处理H9c2心肌细胞组、过表达ALDH2组、酒精处理ALDH2高转染心肌细胞组和酒精+α-LA处理ALDH2高转染心肌细胞组。采用CCK-8实验方法确定酒精以及α-LA的干预细胞浓度;5-乙炔基-2′-脱氧尿嘧啶核苷(5-ethynyl-2'-deoxyurioline,EdU)染色观察各组心肌细胞的增殖活力;二氢乙啶(dihydroethiolium,DHE)染色观察各组心肌细胞活性氧(reactive oxygen species,ROS)表达;Western blot检测各分组心肌细胞内ALDH2、沉默信息调节因子1(silent information regulator 1,SIRT1)、血红素加氧酶1(heme oxygenase 1,HO1)和P53蛋白的表达水平。结果:(1)酒精导致H9c2细胞增殖活力下降,细胞内氧化应激水平升高,表现为细胞内ROS水平升高和相关蛋白(ALDH2、SIRT1和HO1)表达水平下降;而给予α-LA干预可显著减轻酒精诱导的细胞增殖活力下降,降低氧化应激水平。(2)酒精可导致细胞衰老,表现为P53表达升高,而α-LA会逆转P53的高表达。(3)过表达ALDH2也可显著减轻酒精诱导的细胞增殖活力下降,抑制ROS水平升高和氧化应激相关蛋白(ALDH2、SIRT1和HO1)表达下降,以及逆转衰老相关蛋白P53的高表达。结论:α-LA可能通过激活ALDH2来抑制氧化应激和延缓细胞衰老,从而对抗酒精引起的细胞损伤,发挥对心肌细胞的保护作用。

Zinc-α2-glycoprotein 1 attenuates non-alcoholic fatty liver disease by negatively regulating tumour necrosis factor-α

BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.

One-pot Approach to the Conversion of Alcohols into α-Halo-α, β-unsaturated Esters

The sequential oxidation-Horner-Wadsworth-Emmons reaction of alcohols to prepare α-Halo-α,β-unsaturated esters （halo =F, Cl） with middle to excellent （Z）-selectivity was developed.

Synthesis of α-hydroxy ketones by copper（Ⅰ）-catalyzed hydration of propargylic alcohols: CO2 as a cocatalyst under atmospheric pressure

Inexpensive and efficient Cu(Ⅰ) catalysis is reported for the synthesis of α-hydroxy ketones from propargylic alcohols, CO2, and water via tandem carboxylative cyclization and nucleophilic addition reaction. Notably, hydration of propargylic alcohols can be carried out smoothly under atmospheric CO2 pressure, generating a series of α-hydroxy ketones efficiently and selectively. This strategy shows great potential for the preparation of valuable α-hydroxy ketones by using CO2 as a crucial cocatalyst under mild conditions.

Association between serumα-L-fucosidase andnon-alcoholic fatty liver disease:Cross-sectional study

AIM: To explore the association between serum α-Lfucosidase(Af U) and non-alcoholic fatty liver disease(NAf LD).METHODS: A total of 16473 individuals(9456 men and 7017 women) were included in the current study, who presented for a health examination at the first Affiliated hospital of Zhejiang University School of medicine in 2014. The baseline characteristics of the cohort were compared by NAf LD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAf LD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of Af U in the diagnosis of NAf LD.RESULTS: The prevalence rates of NAf LD and metabolic syndrome(met S) were 38.0% and 25.4%, respectively. The NAf LD group had significantly higher Af U levels than the non-NAf LD group(28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAf LD increased with progressively higher serum Af U levels. Af U was positively correlated with met S and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that Af U was associated with an increased risk of NAf LD(OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of Af U for the diagnosis of NAf LD was 27.5 U/L. The area under the curve(diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: Af U level is significantly associated with NAf LD, and elevated Af U level is an independent risk factor for NAf LD.

白藜芦醇通过AMPK/PPARα/PGC1α影响酒精依赖致肝损伤机制研究

目的 观察白藜芦醇(Resveratrol, RES)对酒精依赖大鼠肝组织损伤以及AMP依赖的蛋白激酶(adenosine 5-monophosphate-activated protein, AMPK)/过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptorα,PPARα)/过氧化物酶体增殖物激活受体γ辅激活子1α(peroxisome proliferator activated receptor gamma coactivator 1 alpha, PGC1α)信号通路的影响,讨论RES治疗酒精依赖致肝损伤的修复机制,为临床应用RES提供科学依据。方法 将SPF级雄性大鼠采用随机数字表法设立空白对照组、酒精依赖模型组,采用双瓶自由饮建立20%的酒精依赖模型;酒精依赖模型组制备成功后随机分为酒精依赖模型组、RES高、中、低剂量治疗组,继续给与双瓶自由饮,RES按照100、50、25 mg/(kg·d)剂量灌胃14 d。建模期间检测大鼠体重、饮酒量和饮水量,RES治疗后蛋白免疫印迹法检测大鼠肝组织AMPK、磷酸化AMP依赖的蛋白激酶(phosphorylation-adenosine 5’-monophosphate-activated protein kinas, p-AMPK)、PPARα和PGC1α蛋白表达。结果 蛋白免疫印迹法结果显示:与空白对照组比较,酒精依赖模型组p-AMPK(t=6.61,P<0.05)、PPARα(t=3.08,P<0.05)和PGC1α(t=7.09,P<0.05)表达水平显著下调;与酒精依赖模型组比较,RES高剂量治疗组p-AMPK(F=8.60,P<0.05)、PPARα(F=4.38,P<0.05)和PGC1α(F=11.33,P<0.05)显著上调。结论 结果显示RES可能通过调控AMPK/PPARα/PGC1α信号发挥保护作用。

Effect of Shengsui Jiangu capsule on TNF-α, TGF-β1, and empty bone lacuna in rats with alcoholic osteoporosis

TGF-Objective:To investigate the effect of postgraduate Shengsui Jiangu Capsule on tumor necrosis factors TNF-α,transforming growth factor TGF-β1 and empty bone lacuna in rats with alcoholic osteoporosis.Method:120 SD rats were randomly divided into 4 groups,30 rats in each group:blank group,model group,western medicine control group and traditional Chinese medicine intervention group.Liquor gavage was used to model the disease,except for the blank group.The western medicine control group was gavaged with a suspension of calcium carbonate and afad3,while the Chinese medicine intervention group was gavaged with a suspension of Shengsui Jiangu capsules combined with 0.9%saline solution injection.The values of TNF-αand TGF-β1 in femora were measured after 8,12,and 16 weeks of intervention.After dissecting out the femoral head using the HE(hematoxylin-eosin staining)staining method,the bone lacunae were observed under a light microscope,and the empty bone lacunae rate was calculated for intergroup comparison.Results:Compared with the blank group,the model group had a significantly higher percentage of TNF-αand empty bone lacunae,and a significantly lower percentage of TGF-β1(P<0.01).Compared with the model group,the rates of TNF-αand empty bone lacunae in the western medicine control group and the Chinese medicine intervention group were significantly decreased,and TGF-β1 was significantly increased(P<0.01).The traditional Chinese medicine intervention group was more effective than the western medicine control group(P<0.05).Conclusion:Shengsui Jiangu capsule attenuates the expression of TNF-α,enhances the expression of TGF-β1,decreases the rate of empty bone lacunae,and achieves a protective effect against alcoholic osteoporosis in rats with alcoholic osteoporosis.

Cobalt Incorporated Pyramidal Shaped α-Fe2O3 Nanoparticles from Poly-vinyl Alcohol Based Precursor

Precursor foam based Co incorporated α-Fe2O3 (AFC) was successfully synthesized at 600℃ calcination temperature by simple solution method using PVA. The formation of α-Fe2O3 nanoparticles was confirmed by X-ray diffraction measurement and reduction in crystallite size was found after cobalt incorporation. Field emission scanning electron microscopy revealed the existence of pyramidal shaped iron oxide in AFC. FTIR and Raman spectra also confirmed the presence of α-Fe2O3. Photocatalytic activity study showed that the cobalt incorporated α-Fe2O3 was better photocatalyst than pure α-Fe2O3. The cobalt incorporated iron oxide nanoparticles could be used for drug delivery application and this simple preparation method could be adopted for the synthesis of other transition metal oxides.

Copper-catalyzed tandem radical amination/1,2-carbon migration of allylic alcohols: Direct access to α-quaternary-β-amino ketones

A novel nitrogen‐centered radical‐induced1,2‐carbon migration reaction of allylic alcohols has been developed.This method provides easy access to a variety ofα‐quaternary‐β‐amino ketones under mild reaction conditions.The reaction has a wide substrate scope and operational simplicity.Mechanistic studies suggest that1,2‐carbon migration is induced by regioselective nitrogen‐centered radical addition to the alkene unit.?2018,Dalian Institute of Chemical Physics,Chinese Academy of Sciences.Published by Elsevier B.V.All rights reserved.

Peroxisome proliferator-activated receptor α,a potential therapeutic target for alcoholic liver disease

Alcoholic liver injury represents a progressive process with a range of consequences including hepatic steatosis, steatohepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Targeting key molecular regulators involved in the development of alcoholic liver injury may be of great value in the prevention of liver injury. Peroxisome proliferator-activated receptor &#x003b1; (PPAR&#x003b1;) plays a pivotal role in modulation of hepatic lipid metabolism, oxidative stress, inflammatory response and fibrogenesis. As such, PPAR&#x003b1; may be a potential therapeutic target for the treatment of alcoholic liver disease.

A Facile and Efficient Oxidation of α,β-Unsaturated Alcohols with Manganese Dioxide in Ionic Liquids under Mild Conditions

The oxidation of a,b-unsaturated primary and secondary alcohols to corresponding aldehydes and ketones by manganese dioxide in ionic liquids as a safe recyclable and accelerative reaction medium under mild conditions are described. The rate of the oxidation reaction is faster and the yield is higher than that with conventional procedures.

基于肌醇需求激酶1α/c-Jun氨基末端激酶信号通路探讨胆宁片干预非酒精性脂肪性肝病的作用及机制

目的基于肌醇需求激酶1α/c-Jun氨基末端激酶(IRE1α/JNK)信号通路,探讨胆宁片对非酒精性脂肪性肝病(NAFLD)模型大鼠的作用及机制。方法将32只SD大鼠随机分为正常饮食组(A组,等体积生理盐水,8只)和高脂饮食组(24只);高脂饮食组大鼠喂养10周复制NAFLD模型成功后,再随机分为模型组(B组,等体积生理盐水)、多烯磷脂酰胆碱组[C组,142.5 mg/(kg·d)]和胆宁片组[D组,562.5 mg/(kg·d)],各8只。各组小鼠均灌胃相应药物干预6周。测定大鼠的体质量、血糖(GLU);采用苏木精-伊红染色(HE)法观察大鼠肝组织病理形态变化,采用油红染色法观察肝组织脂质沉积;检测血清胰岛素(INS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(NEFA)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平;采用免疫印迹(Western blot)法检测肝组织IRE1α、JNK1、磷酸化胰岛素受体底物1(p-IRS1)的蛋白表达水平。结果与B组比较,D组大鼠血糖和TC,TG,LDL-C,NEFA,ALT,AST水平均显著降低(P<0.01),血清INS和HDL-C水平显著升高(P<0.01);脂肪变性程度及细胞肿胀明显减轻,脂滴空泡体积缩小,数量减少;肝脏IRE1α,JNK1,p-IRS1蛋白表达水平均显著降低(P<0.01)。结论胆宁片可能通过下调IRE1α/JNK信号通路,减轻肝脏脂肪变性,从而改善NAFLD。

血清PGC-1α、A1AT水平与2型糖尿病合并非酒精性脂肪性肝病发病的关系

目的 探讨血清过氧化物酶体增殖物激活受体γ共激活剂-1α(PGC-1α)、α1-抗胰蛋白酶(A1AT)水平与2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)发病的关系。方法 选取T2DM患者184例(T2DM组),另选取同期60名体检健康志愿者(对照组),根据是否合并NAFLD将T2DM患者分为NAFLD组(95例)和非NAFLD组(89例)。采用酶联免疫吸附法检测血清PGC-1α、A1AT水平。多因素Logistic回归分析影响T2DM合并NAFLD的因素,受试者工作特征曲线分析血清PGC-1α、A1AT水平对T2DM合并NAFLD的预测价值。结果 与对照组比较,T2DM组血清PGC-1α、A1AT水平降低(P均<0.05)。与非NAFLD组比较,NAFLD组血清PGC-1α、A1AT水平降低(P均<0.05)。体质量指数增加、T2DM病程延长、高血压和总胆固醇、甘油三酯、低密度脂蛋白胆固醇、谷草转氨酶、谷丙转氨酶升高为T2DM合并NAFLD的独立危险因素,高密度脂蛋白胆固醇、PGC-1α、A1AT升高为独立保护因素(P均<0.05)。血清PGC-1α、A1AT水平联合预测T2DM合并NAFLD的曲线下面积为0.885,大于血清PGC-1α、A1AT水平单独预测的0.788、0.786(P均<0.05)。结论 血清PGC-1α、A1AT水平降低与T2DM合并NAFLD发病密切相关,血清PGC-1α、A1AT水平联合对T2DM合并NAFLD具有较高的预测价值。

血清AMPK-αmRNA、Caspase-6 mRNA水平对非酒精性脂肪肝疗效的预测价值及影响因素分析

目的 分析血清腺苷酸活化蛋白激酶-αmRNA(Adenosine monophosphate activated protein kinase α,AMPK-αmRNA)、半胱氨酸天冬氨酸蛋白酶-6(Cystein-asparate protease,caspase-6) mRNA水平对非酒精性脂肪肝(Non-alcoholic fatty liver disease,NAFLD)疗效的预测价值及影响因素。方法 选取2021年10月-2023年8月聊城市人民医院感染性疾病科收治的188例NAFLD患者为研究对象,治疗6个月后以甘油三酯(TG)降低≥20%和(或)总胆固醇(TC)降低≥10%判断为治疗有效,归入有效组,否则判断为治疗无效,归入无效组。所有患者治疗前后检测血清AMPK-αmRNA、Caspase-6 mRNA水平。收集NAFLD患者一般资料,分析NAFLD疗效的影响因素。绘制受试者工作特征(Receiver operating characteristic curve,ROC)曲线分析血清AMPK-αmRNA,Caspase-6 mRNA水平对NAFLD疗效的预测价值。结果 188例NAFLD患者治疗6个月脱落6例,有效随访182例,其中治疗有效126例(69.23%),纳入有效组,治疗无效56例(30.77%),纳入无效组。与本组治疗前比较,治疗6个月后患者血清AMPK-αmRNA水平升高,Caspase-6 mRNA水平降低,差异有统计学意义(P<0.05)。与无效组比较,有效组治疗前、治疗6个月血清AMPK-αmRNA水平升高,Caspase-6 mRNA水平降低,差异有统计学意义(P<0.05)。患有糖尿病,血清TC、TG、低密度脂蛋白胆固醇(Low-density lipoprotein,LDL-C)、谷丙转氨酶(Alanime aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST),Caspase-6 mRNA水平是NAFLD疗效的独立危险因素,治疗前血清AMPK-αmRNA水平是其独立保护因素(P<0.05)。建立Logistic回归模型:logit(P)=-29.182-0.867×AMPK-αmRNA+0.890×Caspase-6 mRNA+1.956×糖尿病+1.283×TG+0.982×TC+0.703×LDL-C+0.066×ALT+0.101×AST,拟合度较好。治疗前血清AMPK-αmRNA、Caspase-6 mRNA水平及Logistic回归模型预测NAFLD疗效的曲线下面积(Area under curve,AUC)值分别为0.757、0.717、0.816,Logistic回归模型的预测价值大于AMPK-αmRNA,Caspase-6 mRNA单独评估价值(Z=2.149,P=0.032;Z=2.879,P=0.004)。结论 患者是否患有糖尿病,血清TG、TC、LDL-C、ALT、AST、AMPK-αmRNA、Caspase-6 mRNA水平是NAFLD疗效的影响因素,检测血清AMPK-αmRNA、Caspase-6 mRNA水平对NAFLD疗效具有一定预测价值。

MAGNESIUM-NETHAN0L REDUCTION OF 2-(1, 3-DITHIAN-2-YLIDENE)-I-ARYL KETONES:A FACILE ROUTE TO α-ARYL-β-(1,3-DITHANE)ALCOHOLS

In a facile procedure, 2-(1, 3-dithian-2-ylidene)-l-aryl ketones 1 vere reduced with magnesium in methanol to give α-aryl-β -(1, 3-dithane) alcohols 2 in good to high yields.

生髓健骨胶囊对酒精性骨质疏松症患者的血清IL-6、TNF-α因子的影响

目的探讨生髓健骨胶囊对治疗酒精性骨质疏松症患者的IL-6、TNF-α因子水平的影响。方法收集黑龙江中医药大学附属第一医院骨伤科2022年6月至2023年8月54例符合AOP的患者作为研究对象,并且采用随机数字表法分为治疗组和对照组,每组各27例。治疗组予患者口服碳酸钙维D3、生髓健骨胶囊治疗;对照组予患者口服碳酸钙维D3与阿仑膦酸钠片,3个月为1个疗程,连续治疗3个疗程。比较两组患者治疗前后腰椎和左髋BMD骨密度及血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平变化。结果治疗后,治疗组腰椎和左髋BMD骨密度分别为(0.757±0.018)、(0.646±0.028)g/cm^(2),明显高于对照组的(0.743±0.022)、(0.632±0.014)g/cm^(2),差异均有统计学意义(P<0.05);治疗组血清IL-6、TNF-α分别为(44.90±10.16)、(59.53±9.35)n g/L,明显低于对照组的(59.97±10.48)、(77.89±10.61)ng/L,差异均有统计学意义(P<0.05)。结论生髓健骨胶囊对于治疗酒精性骨质疏松的临床疗效明确,可以明显改善患者腰椎和左髋BMD骨密度,其机制可能是通过调节血清中IL-6和TNF-α的浓度从而影响骨吸收。

α-甲基丙烯酸十四酯-十六烯降凝剂的合成及其降凝效果

用α-甲基丙烯酸和十四醇合成了α-甲基丙烯酸十四酯(TDMA);以甲苯为溶剂、过氧化苯甲酰(BPO)为引发剂,TDMA与十六烯(HE)共聚生成了降凝剂α-甲基丙烯酸十四酯-十六烯二元共聚物(AH);对TDMA和AH进行了红外光谱表征;考察了影响AH降凝效果的主要因素以及将AH与两种市售降凝剂分别复配后的降凝效果。实验结果表明,以在n(TDMA)∶n(HE)=6∶1、BPO用量(相对于单体TDMA和HE的质量分数)1.0%、甲苯用量(相对于单体TDMA和HE的质量分数)75%、聚合时间5h的条件下合成的AH为降凝剂,在AH用量(相对于基础油的质量分数)为0.5%时,AH的降凝效果最佳,可使燕山500SN、燕山200SN、河南、湖南和大庆5种基础油的凝点分别降低29,31,20,6,18℃;AH与市售降凝剂复配后,复配物对基础油的降凝效果基本优于单独使用市售降凝剂的降凝效果。

木香槟榔丸全方对小鼠肿瘤坏死因子α含量和胃蛋白酶原的影响

目的:观察木香槟榔丸全方对小鼠肿瘤坏死因子α(TNF-α)和胃蛋白酶原(PG)的影响,探讨木香槟榔丸全方对小鼠酒精性胃损伤的防治作用。方法:小鼠60只随机分为空白对照组(A组)12只、模型对照组(B组)24只、木香槟榔丸干预组(C组)24只。常规饲料喂养,A组灌胃生理盐水,B组灌胃56°白酒和生理盐水,C组灌胃56°白酒和木香槟榔丸全方冲剂,每24 h 1次,持续1周。每日观察记录小鼠的摄食、饮水量及体重,实验结束时检测小鼠胃匀浆中胃蛋白酶原(PGⅠ、PGⅡ)浓度及血中肿瘤坏死因子(TNF-α)浓度。结果:A组小鼠几乎无躁动,进食饮水如常,行动灵活,体重增长在正常范围内,毛发明亮且有光泽;B组小鼠明显不安烦躁,少进食,毛发几乎无光泽,呈灰黄色,排干样便,处死后发现其胃部出现明显胀气、出血倾向;C组小鼠毛发润泽度对比B组较好,排软样便。与B组相比,A组和C组PGⅠ的浓度明显较高,PGⅡ的浓度明显降低(P<0.05),TNF-α浓度显著降低(P<0.05)。结论:木香槟榔丸全方对小鼠酒精性胃损伤具有良好的预防和治疗作用。

血清半乳糖凝聚素-3、α-klotho表达与代谢相关脂肪性肝病糖脂水平及预后的关系

目的 探讨半乳糖凝聚素-3(Gal-3)、α-klotho在代谢相关脂肪性肝病(MAFLD)病人血清中的表达情况,并分析其与糖脂水平和预后的关系。方法 选取2020年12月至2021年12月来保定市人民医院就诊并确诊为MAFLD病人112例为研究对象,根据非酒精性脂肪性肝病肝纤维化评分(NAFLDFS)将病人分为肝纤维化危险组(n=46)、无肝纤维化组(n=66),同时选取50例健康者为对照组。收集研究对象一般资料,采用酶联免疫吸附法对血清中α-klotho、Gal-3表达水平进行检测,Pearson法分析α-klotho、Gal-3表达的相关性,及两者分别与糖脂代谢指标的相关性;受试者操作特征(ROC)曲线分析血清α-klotho、Gal-3水平对MAFLD病人预后的预测价值。结果 MAFLD病人血清中α-klotho表达水平低于对照组(268.15±82.13)ng/L,Gal-3表达水平高于对照组(1.48±0.47)μg/L,其中肝纤维化危险组病人血清中α-klotho表达水平低于无肝纤维化组[(140.49±45.16)ng/L比(215.51±70.33)ng/L],Gal-3表达水平高于无肝纤维化组[(2.26±0.50)μg/L比(1.96±0.33)μg/L](P<0.05);预后不良的MAFLD病人血清中α-klotho表达水平低于预后良好病人,Gal-3高于预后良好病人,均差异有统计学意义(P<0.05)。Pearson法分析结果显示,MAFLD病人血清中α-klotho、Gal-3表达呈显著负相关(r=-0.49,P<0.05);MAFLD病人血清中α-klotho表达与空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗(HOMA-IR)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-c)、天冬氨酸转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转肽酶(GGT)表达呈负相关,与高密度脂蛋白胆固醇(HDL-c)、血小板(PLT)、血清白蛋白(Alb)表达呈正相关(P<0.05);Gal-3表达与FBG、FINS、HOMA-IR、TC、TG、LDL-c、AST、ALT、GGT表达呈正相关,与HDL-c、PLT、Alb表达呈负相关(P<0.05)。ROC曲线结果显示,血清α-klotho、Gal-3水平评估预后不良病人的曲线下面积(AUC)分别为0.83、0.84,对应的灵敏度分别为86.84%、80.90%,特异度分别为66.22%、82.02%;二者联合评估的AUC为0.93,灵敏度为86.84%,特异度为89.19%。结论 MAFLD病人血清中α-klotho表达降低,Gal-3表达升高,二者表达与糖脂水平和病人预后密切相关。

非酒精性脂肪性肝病患者血清HIF-1α、HMGB1和脂联素水平变化及其与颈动脉粥样硬化的关系研究

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清低氧诱导因子-1α(HIF-1α)、高迁移率族蛋白1(HMGB1)和脂联素(APN)水平变化及其与颈动脉粥样硬化(CAS)的关系。方法2018年5月~2023年3月我院诊治的NAFLD患者158例(其中合并CAS者71例),使用Fibrotouch弹性成像仪诊断脂肪肝,使用超声诊断仪检测颈动脉斑块形成。采用ELISA法检测血清HIF-1α、HMGB1和APN水平,应用二元Logistic回归分析NAFLD合并CAS的影响因素,应用受试者工作特征曲线下面积(AUC)评估血清指标预测NAFLD患者合并CAS的效能。结果合并CAS组收缩压为(137.1±10.3)mmHg,显著高于未合并CAS组【(132.9±8.2)mmHg,P<0.05】;合并CAS组血清TC、LDL-C、HIF-1α和HMGB1水平分别为(6.5±2.3)mmol/L、(3.7±0.6)mmol/L、(25.7±6.5)pg/L和(9.4±2.3)ng/ml,显著高于未合并CAS组【分别(5.1±1.7)mmol/L、(2.8±0.3)mmol/L、(17.2±4.1)pg/L和(6.1±1.5)ng/ml,P<0.05】,而血清APN为(7.5±3.0)mg/L,显著低于未合并CAS组【(12.8±4.6)mg/L,P<0.05】;多因素Logistic回归分析显示,TC(OR=1.411,95%CI:1.133~1.757)、LDL-C(OR=1.419,95%CI:1.128~1.785)、HIF-1α(OR=1.504,95%CI:1.182~1.914)、HMGB1(OR=1.520,95%CI:1.206~1.916)和APN(OR=1.530,95%CI:1.226~1.909)均是影响NAFLD患者合并CAS的独立危险因素(P<0.05);ROC曲线分析显示,血清HIF-1α、HMGB1和APN水平联合预测NAFLD患者合并CAS的AUC为0.863,其敏感度为94.5%,特异度为75.0%,优于各指标单独预测(P<0.05)。结论NAFLD患者血清HIF-1α和HMGB1水平升高而血清APN水平降低是发生CAS的危险因素,应及时发现和给予必要的干预。